The fetoplacental circulation is a critical component to normal fetal growth and development. Abnormal blood flow within this vascular system is often found in conjunction with fetal growth restriction as demonstrated by umbilical artery and vein Doppler indices. These changes increase risk for stillbirth, and preterm delivery is often warranted in order to avoid this outcome. Furthermore, preterm neonates with growth restriction tend to demonstrate more severe manifestations of prematurity than their age-matched, appropriately-grown counterparts. Long- term consequences of growth restriction are just as concerning, with strong evidence of increased risks for cardiovascular disease, metabolic syndrome, and obesity in adulthood. Our long-term research goal is to determine the molecular mechanisms responsible for dysfunction of placental endothelial cells (i.e., the cells lining the fetoplacental vessels) in pregnancies complicated by fetal growth restriction. These studies will be performed in the primary mentor's (Dr. Serdar Bulun) laboratory, with the input of other mentors, collaborators, and consultants (Dr. Douglas Losordo, Dr. Ronald Magness, Dr. Linda Ernst). The goal of this research training plan is to establish the ability to become an independent investigator. In total, we anticipate that these studies will contribute critical knowledge in better understanding the changes that occur within these vessels in the setting of fetal growth restriction and hopefully provide targets for prevention and therapy in the future.